Project Summary/Abstract The long-term objective of this research is to enhance the capabilities of echocardiography as a primary imaging modality for the definitive quantification of cardiac properties and assessment of function needed for optimal diagnoses. Clinical applications of cardiac diagnostic ultrasound require imaging with the sound propagating at varying angles relative to the predominant myocardial fiber orientation. Consequently, variation of ultrasonic properties with the direction of propagation in tissue, i.e., anisotropy, is a significant factor in clinical echocardiography. Promising areas of application of cardiac ultrasound such as myocardial strain and strain-rate imaging, contrast echocardiography, and myocardial tissue characterization are all subject to effects arising from the anisotropic properties of myocardium. Underlying all of the studies associated with this research is the assertion that a better understanding of the fundamental mechanisms underlying the observed anisotropic ultrasonic properties of myocardium, and the consequences of altered anisotropic properties of diseased hearts, will facilitate and enhance the role of ultrasound in the non-invasive detection and quantification of the extent and severity of specific pathologies in the clinical arena. Hence, the specific goals of this research are to identify the mechanisms contributing to the observed anisotropy of the intrinsic ultrasonic properties of myocardium and to develop approaches for exploiting the effects of anisotropy in echocardiographic-based assessments of the hearts of patients. In order to focus the research effort, a special emphasis has been placed on studies designed to investigate the effects of altered myocardial architecture (i.e., altered anisotropy) associated with hypertrophic cardiomyopathy on echocardiographic imaging and tissue characterization. To achieve these goals, the following Specific Aims have been identified to provide a basis for improving the diagnostic power of ultrasonics: 1) Identify mechanisms contributing to the observed anisotropy in ultrasonic backscatter, attenuation, and velocity of myocardium;and 2) Develop strategies for exploiting opportunities and overcoming potential stumbling blocks arising from anisotropy in echocardiographic imaging and myocardial assessment in normal and diseased hearts. Studies designed to address these Specific Aims include: measurements of excised myocardial specimens to provide the intrinsic ultrasonic scattering and attenuation properties over a broad bandwidths;measurements and the development of models associated with the identification of effective scatterer characteristics and viscoelastic properties responsible for the observed anisotropy of properties;investigations of the effects of myocardial anisotropy on harmonic imaging;development of a polar backscatter method of measuring the transmural myofiber orientation;and measurements investigating how the degree of altered myocardial structure and properties due to hypertrophic cardiomyopathy affect the ultrasonic backscatter and attenuation properties and the development of methods for assessing these altered properties in patients.Project Narrative Relevance: Results of this research will enhance the capabilities of ultrasonic imaging of the heart as an effective tool in aiding diagnoses of heart disease. Because the microstructural properties of the heart can significantly influence the ultrasonic properties and, therefore, ultrasonic images, a better understanding of the nature of these properties will provide new insights into the use of ultrasound to characterize features of diseased hearts.